Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4.

The effects of insulin, T4, and T3 treatment on cardiac function, myosin ATPase activity, and myosin isozyme distribution were studied in alloxan diabetic rats. Diabetes resulted in depressed peak ventricular pressure development, heart rate, and left ventricular +dP/dt. Myocardial Ca2+-activated myosin ATPase activity was reduced in association with lower serum levels of T3 and T4. The V1 isozyme of myosin decreased, and both V2 and V3 isozymes increased. Insulin treatment totally reversed the changes in function, serum thyroid hormones, and myosin ATPase activity. Treatment of diabetic animals with T4 (5 or 10 micrograms/day) prevented the decrease in myosin ATPase but did not prevent the changes in cardiac function, myosin isozymes, or serum T3 levels. Pharmacological doses of T3 (3 micrograms/day) that were adequate to maintain higher than normal serum T3 corrected the decrease in Ca2+-activated myosin ATPase and heart rate but only partially corrected the changes in pressure development and myosin isozyme distribution. Only when serum T3 was increased to four times normal was cardiac function corrected.